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Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population

Published online by Cambridge University Press:  05 July 2016

Bradley S. Marino ,
David J. Goldberg ,
Adam L. Dorfman ,
Eileen King ,
Heidi Kalkwarf ,
Babette S. Zemel ,
Margaret Smith ,
Jesse Pratt ,
Mark A. Fogel  and
Amanda J. Shillingford
...Show all authors
Bradley S. Marino*
Affiliation:
Department of Pediatrics, Division of Cardiology, Division of Critical Care Medicine, Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
David J. Goldberg
Affiliation:
Department of Pediatrics, Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania United States of America
Adam L. Dorfman
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, University of Michigan C.S. Mott Children’s Hospital, Ann Arbor, Michigan, United States of America
Eileen King
Affiliation:
Department of Pediatrics, Division of Biostatistics & Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Heidi Kalkwarf
Affiliation:
Department of Pediatrics, Division of General and Community Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Babette S. Zemel
Affiliation:
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America
Margaret Smith
Affiliation:
Department of Pediatrics, Division of Cardiology, Division of Critical Care Medicine, Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Jesse Pratt
Affiliation:
Department of Pediatrics, Division of Biostatistics & Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Mark A. Fogel
Affiliation:
Department of Pediatrics, Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania United States of America
Amanda J. Shillingford
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin, United States of America
Barbara J. Deal
Affiliation:
Department of Pediatrics, Division of Cardiology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois United States of America
Anitha S. John
Affiliation:
Department of Pediatrics, Division of Cardiology, The Mayo Clinic, Rochester, Minnesota, United States of America
Caren S. Goldberg
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, University of Michigan C.S. Mott Children’s Hospital, Ann Arbor, Michigan, United States of America
Timothy M. Hoffman
Affiliation:
Department of Pediatrics, Division of Cardiology, Nationwide Children’s Hospital, Columbus Ohio, United States of America
Marshall L. Jacobs
Affiliation:
Department of Pediatric and Congenital Heart Surgery, Cleveland Clinic, Cleveland, Ohio, United States of America
Asher Lisec
Affiliation:
Department of Pediatrics, Division of Cardiology, Division of Critical Care Medicine, Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Susan Finan
Affiliation:
Department of Pediatrics, Division of Cardiology, Division of Critical Care Medicine, Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Lazaros K. Kochilas
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, University of Minnesota Amplatz Children’s Hospital, Minneapolis, Minnesota, United States of America
Thomas W. Pawlowski
Affiliation:
Department of Pediatrics, Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania United States of America
Kathleen Campbell
Affiliation:
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Clinton Joiner
Affiliation:
Department of Pediatrics, Division of Hematology/Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Stuart L. Goldstein
Affiliation:
Department of Pediatrics, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Paul Stephens Jr
Affiliation:
Department of Pediatrics, Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania United States of America
Alvin J. Chin
Affiliation:
Department of Pediatrics, Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania United States of America
*
Correspondence to: B. S. Marino, MD, MPP, MSCE, Professor of Pediatrics and Medical Social Sciences, Northwestern University Feinberg School of Medicine, Heart Center Co-Director, Research and Academic Affairs, Divisions of Cardiology and Critical Care Medicine, Ann and Robert H. Lurie Children’s Hospital of Chicago, 225 East Chicago Avenue, Box 21, Chicago, IL 60611-2991, United States of America. Tel: +312 227 4373; Fax: +312 227 9640; E-mail: bradley.marino@northwestern.edu
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Abstract

Background

Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients.

Methods and results

This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman’s Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6–33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (−0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (−0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63–0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].

Conclusions

Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.

Keywords

Fontancardiac MRIbiomarkerscardiac index
Type
Original Articles
Information
Cardiology in the Young , Volume 27 , Issue 1 , January 2017 , pp. 59 - 68
Copyright
© Cambridge University Press 2015 

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References

1. Mahle, WT, Spray, TL, Wernovsky, G, Gaynor, JW, Clark, BJ 3rd. Survival after reconstructive surgery for hypoplastic left heart syndrome: a 15-year experience from a single institution. Circulation 2000; 102: III136–141.Google Scholar
2. Tweddell, JS, Ghanayem, NS, Mussatto, KA, et al. Mixed venous oxygen saturation monitoring after stage 1 palliation for hypoplastic left heart syndrome. Ann Thorac Surg 2007; 84: 1301–1310; discussion 1310–1301.Google Scholar
3. Mainwaring, RD, Lamberti, JJ, Uzark, K, Spicer, RL, Cocalis, MW, Moore, JW. Effect of accessory pulmonary blood flow on survival after the bidirectional Glenn procedure. Circulation 1999; 100: II151–156.Google Scholar
4. Khairy, P, Fernandes, SM, Mayer, JE Jr, et al. Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery. Circulation 2008; 117: 85–92.CrossRefGoogle ScholarPubMed
5. Schwartz, MC, Sullivan, L, John, AS, et al. Hepatic fibrosis in Fontan patients correlates with pre-Fontan morbidity. J Am Coll Cardiol 2011; 57: E411.Google Scholar
6. Mavroudis, C, Deal, BJ, Backer, CL, et al. Maxwell Chamberlain memorial paper for congenital heart surgery. 111 Fontan conversions with arrhythmia surgery: surgical lessons and outcomes. Ann Thorac Surg 2007; 84: 1457–1465; discussion 1465–1456.Google Scholar
7. Jayakumar, KA, Addonizio, LJ, Kichuk-Chrisant, MR, et al. Cardiac transplantation after the Fontan or Glenn procedure. J Am Coll Cardiol 2004; 44: 2065–2072.Google Scholar
8. Schumacher, KR, Stringer, KA, Donohue, JE, et al. Fontan-associated protein-losing enteropathy and plastic bronchitis. The Journal of Pediatrics 2015; 166: 970–977.Google Scholar
9. Chin, AJ, Stephens, P, Goldmuntz, E, Leonard, MB. Serum alkaline phosphatase reflects post-Fontan hemodynamics in children. Pediatr Cardiol 2009; 30: 138–145.Google Scholar
10. Kaushansky, K. Lineage-specific hematopoietic growth factors. N Engl J Med 2006; 354: 2034–2045.Google Scholar
11. Collins, N, Piran, S, Harrison, J, Azevedo, E, Oechslin, E, Silversides, CK. Prevalence and determinants of anemia in adults with complex congenital heart disease and ventricular dysfunction (subaortic right ventricle and single ventricle physiology). Am J Cardiol 2008; 102: 625–628.CrossRefGoogle ScholarPubMed
12. Whitehead, KK, Gillespie, MJ, Harris, MA, Fogel, MA, Rome, JJ. Noninvasive quantification of systemic-to-pulmonary collateral flow: a major source of inefficiency in patients with superior cavopulmonary connections. Circ Cardiovasc Imaging 2009; 2: 405–411.Google Scholar
13. Mosteller, RD. Simplified calculation of body-surface area. N Engl J Med 1987; 317: 1098.Google Scholar
14. Schwartz, GJ, Brion, LP, Spitzer, A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 1987; 34: 571–590.Google Scholar
15. Van Hoof, VO, Hoylaerts, MF, Geryl, H, Van Mullem, M, Lepoutre, LG, De Broe, ME. Age and sex distribution of alkaline phosphatase isoenzymes by agarose electrophoresis. Clin Chem 1990; 36: 875–878.CrossRefGoogle ScholarPubMed
16. Schwartz, MC, Sullivan, L, Cohen, MS, et al. Hepatic pathology may develop before the Fontan operation in children with functional single ventricle: an autopsy study. J Thorac Cardiovasc Surg 2012; 143: 904–909.Google Scholar
17. Kiesewetter, CH, Sheron, N, Vettukattill, JJ, et al. Hepatic changes in the failing Fontan circulation. Heart 2007; 93: 579–584.Google Scholar
18. Poelzl, G, Ess, M, Mussner-Seeber, C, Pachinger, O, Frick, M, Ulmer, H. Liver dysfunction in chronic heart failure: prevalence, characteristics and prognostic significance. Eur J Clin Invest 2012; 42: 153–163.Google Scholar
19. Camposilvan, S, Milanesi, O, Stellin, G, Pettenazzo, A, Zancan, L, D’Antiga, L. Liver and cardiac function in the long term after Fontan operation. Ann Thorac Surg 2008; 86: 177–182.CrossRefGoogle Scholar
20. Ronco, C, McCullough, PA, Anker, SD, et al. Cardiorenal syndromes: an executive summary from the consensus conference of the acute dialysis quality initiative (ADQI). Contrib Nephrol 2010; 165: 54–67.Google Scholar
21. National kidney foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39: S1–S266.Google Scholar
22. Al-Ahmad, A, Rand, WM, Manjunath, G, et al. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 2001; 38: 955–962.Google Scholar
23. Dries, DL, Exner, DV, Domanski, MJ, Greenberg, B, Stevenson, LW. The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol 2000; 35: 681–689.Google Scholar
24. McAlister, FA, Ezekowitz, J, Tonelli, M, Armstrong, PW. Renal insufficiency and heart failure: prognostic and therapeutic implications from a prospective cohort study. Circulation 2004; 109: 1004–1009.Google Scholar
25. Anand, IS. Anemia and chronic heart failure implications and treatment options. J Am Coll Cardiol 2008; 52: 501–511.Google Scholar
26. Nanas, JN, Matsouka, C, Karageorgopoulos, D, et al. Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol 2006; 48: 2485–2489.Google Scholar
27. Opasich, C, Cazzola, M, Scelsi, L, et al. Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 2005; 26: 2232–2237.CrossRefGoogle ScholarPubMed
28. Jankowska, EA, Rozentryt, P, Witkowska, A, et al. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J 2010; 31: 2232–2237.Google Scholar
29. Powell, AJ, Geva, T. Blood flow measurement by magnetic resonance imaging in congenital heart disease. Pediatr Cardiol 2000; 21: 47–58.Google Scholar
30. Powell, AJ, Maier, SE, Chung, T, Geva, T. Phase-velocity cine magnetic resonance imaging measurement of pulsatile blood flow in children and young adults: in vitro and in vivo validation. Pediatr Cardiol 2000; 21: 104–110.Google Scholar
31. Schaefer, WM, Lipke, CSA, Standke, D, et al. Quantification of left ventricular volumes and ejection fraction from gated 99mTc-MIBI SPECT: MRI validation and comparison of the emory cardiac tool box with QGS and 4D-MSPECT. J Nucl Med 2005; 46: 1256–1263.Google Scholar
32. Chin, AJ, Whitehead, KK, Watrous, RL. Insights after 40 years of the Fontan operation. World J Pediatr Congenit Heart Surg 2010; 1: 328–343.Google Scholar
33. Goldberg, DJ, French, B, McBride, MG, et al. Impact of oral sildenafil on exercise performance in children and young adults after the Fontan operation: a randomized, double-blind, placebo-controlled, crossover trial. Circulation 2011; 123: 1185–1193.Google Scholar
34. Seikaly, MG, Browne, R, Bajaj, G, Arant, BS Jr. Limitations to body length/serum creatinine ratio as an estimate of glomerular filtration in children. Pediatr Nephrol 1996; 10: 709–711.Google Scholar